Immediate Goals: To determine the role of environmental and genetic factors on the development of both bronchiolitis and asthma, with the goal of designing and implementing more effective preventive therapies to reduce the incidence and severity of both infant viral infections and childhood asthma. Career Development Goals: To provide sufficient time for mentoring and research activities. Research Project: Asthma is thought to result from host (genetic) and environment interactions. Viral infections are one important, and modifiable environmental factor that have been established to be important causes of asthma exacerbations in both children and adults; lower respiratory tract infections (LRTI), caused by viruses such as respiratory syncytial virus (RSV) and rhinovirus (RV), are a leading cause of bronchiolitis in infants. Infants hospitalized with bronchiolitis are at significantly increased risk for both recurrent wheezing and childhood asthma. It is not known whether viral respiratory infections directly contribute to asthma causation or simply identify persons at risk for subsequent wheezing. Thus, many possible determinants exist that may contribute to the severity of bronchiolitis and the subsequent development of asthma. This proposal uses a combined, parallel clinical and experimental approach to evaluate the contribution of, causality, and mechanism of how viruses contribute to asthma causation and natural history, all relating to the central hypothesis that viruses, as one significant environmental factor, alter the risk for developing asthma, as well as the natural history of prevalent disease. Specific testable questions related to this hypothesis include: 1) the respiratory viral pathogen, environmental factors, and timing of infection during infancy impact the risk of developing childhood asthma; 2) lower respiratory viral infection during infancy, and the severity of that infection correlates with an increased risk of childhood asthma; 3) allelic variations at genes involved with severity of respiratory viral infection will correlate with a predisposition or resistance to both infant bronchiolitis and childhood asthma. The aims of the mentored award will be met by allowing the PI to translate her experimental expertise to direct clinical studies of progression and functional outcome of childhood viral illness and asthma, with the next goal to make the transition from risk factor determination to intervention and disease prevention.